1. Field of Invention
Methods of treating insufficiencies in hematosis such as hypoxemia, cardiac insufficiency, polyglobulia, and pharmaceutical compositions particularly adapted for use in such method.
2. Prior Art
The compound almitrine, as well as its pharmaceutically-acceptable acid addition salts, are known compounds which have been disclosed in French Pat. No. 2,019,646 and corresponding U.S. Pat. No. 3,647,794. These compounds have been disclosed as respiratory analeptics for treatment of respiratory insufficiencies in relatively high doses, representatively 1 to 5 mg/kg/day orally and 0.1 to 3.0 mg/kg/day intravenously in animals. The compound almitrine is also known as "DCI" and has the chemical name bis-4,6-(allylamino)-2{[bis-(4fluoro-phenyl)methyl]-4-piperazinyl}-triazin e. Of particular interest according to the present invention is its bismethane sulfonate, as well as other pharmaceutically-acceptable acid addition salts thereof.
According to the "Vidal Dictionary" (a 1980 edition), pages 1295 and 1296, the compound almitrine is described under the brand name "Vectarion", a pharmaceutical specially named for almitrine, and recommends 1 to 3 mg/kg/day by perfusion for respiratory resuscitation or 0.5 to 1 mg/kg/day by slow direct intravenous drip for anesthesiology.
In such doses, almitrine increases ventilation and respiratory rate and decreases the amount of carbon dioxide in the arterial blood, the mechanism of action then taking place on peripheral receptors of the respiratory system as indicated in the foregoing cited patents. It has also been indicated there that, in such doses, almitrine has a vascular effect which enables it to maintain the blood flow despite hyperventilation. Further, in accord with the Vidal Dictionary, almitrine corrects disturbances in partial oxygen pressure and partial carbon dioxide pressure as well as in the pH. Finally, almitrine, in these doses, enables the correction of respiratory insufficiency, and therefore constitutes a respiratory analeptic which is used essentially for shock treatment inasmuch as, at the said high dosages, a muscular fatigue presents a serious side effect for a patient treated therewith. This muscular fatigue appears to result from the fact that almitrine acts upon chemical receptors in the aortic and carotid glomeruli through bulbo-protuberantial respiratory zones on muscles producing the respiratory movements, and previous employment of almitrine has been limited by the seriousness of such side effects.